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Ionically crosslinked Ad/chitosan nanocomplexes processed by electrospinning for targeted cancer gene therapy

Authors
 Yeonah Park  ;  Eunah Kang  ;  Oh-Joon Kwon  ;  Taewon Hwang  ;  Hongkwan Park  ;  Jung Min Lee  ;  Jung Hyun Kim  ;  Chae-Ok Yun 
Citation
 JOURNAL OF CONTROLLED RELEASE, Vol.148(1) : 75-82, 2010 
Journal Title
 JOURNAL OF CONTROLLED RELEASE 
ISSN
 0168-3659 
Issue Date
2010
MeSH
Adenoviridae/genetics* ; Animals ; Chitosan/administration & dosage ; Chitosan/chemistry* ; Folic Acid/chemistry ; Gene Transfer Techniques* ; Genetic Therapy* ; Humans ; Mice ; Microscopy, Electron, Transmission ; Neoplasms/therapy* ; Polyethylene Glycols/chemistry
Keywords
Adenovirus ; Chitosan ; Poly(ethylene glycol) ; Folic acid ; Electrospinning
Abstract
For effective cancer gene therapy, systemic administration of tumor-targeting adenoviral (Ad) complexes is critical for delivery to both primary and metastatic lesions. Electrospinning was used to generate nanocomplexes of Ad, chitosan, poly(ethylene glycol) (PEG), and folic acid (FA) for effective FA receptor-expressing tumor-specific transduction. The chemical structure of the Ad/chitosan-PEG-FA nanocomplexes was characterized by NMR and FT-IR, and the diameter and surface charge were analyzed by dynamic light scattering and zeta potentiometry, respectively. The average size of Ad/chitosan-PEG-FA nanocomplexes was approximately 140 nm, and the surface charge was 2.1 mV compared to -4.9 mV for naked Ad. Electron microscopy showed well-dispersed, individual Ad nanocomplexes without aggregation or degradation. Ad/chitosan nanocomplexes retained biological activity without impairment of the transduction efficiency of naked Ad. The transduction efficiency of Ad/chitosan-PEG-FA was increased as a function of FA ratio in FA receptor-expressing KB cells, but not in FA receptor-negative U343 cells, demonstrating FA receptor-targeted viral transduction. In addition, the transduction efficiency of Ad/chitosan-PEG-FA was 57.2% higher than chitosan-encapsulated Ad (Ad/chitosan), showing the superiority of FA receptor-mediated endocytosis for viral transduction. The production of inflammatory cytokine, IL-6 from macrophages was significantly reduced by Ad/chitosan-PEG-FA nanocomplexes, implying the potential for use in systemic administration. These results clearly demonstrate that cancer cell-targeted viral transduction by Ad/chitosan-PEG-FA nanocomplexes can be used effectively for metastatic tumor treatment with reduced immune reaction against Ad.
Full Text
http://www.sciencedirect.com/science/article/pii/S016836591000475X
DOI
10.1016/j.jconrel.2010.06.027
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
Yonsei Authors
Kwon, Oh Joon(권오준)
Park, Yeon Ah(박연아)
Yun, Chae Ok(윤채옥)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/102539
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